Background Psoriasis is a chronic inflammatory skin disorder often associated with obesity. Adiponectin, an anti-inflammatory protein-hormone secreted by adipose tissue, may be a link between obesity and psoriasis. We hypothesized that low plasma adiponectin is associated with an increased risk of psoriasis in observational and causal genetic studies. Methods In observational analyses, we used information on plasma adiponectin and psoriasis in 30 045 individuals from the Copenhagen General Population Study (CGPS). In one-sample Mendelian randomization analyses, we used genetic information on adiponectin and psoriasis in 107 308 individuals from the CGPS. In two-sample Mendelian randomization analyses, we used genetic information on adiponectin from the ADIPOGen consortium and genetic information on psoriasis in 373 338 and 462 933 individuals from the FinnGen study and UK Biobank (UKB). Results In observational analyses, a 1-unit log-transformed higher plasma adiponectin was associated with a hazard ratio (HR) for psoriasis of 0.67 (95% confidence interval: 0.48–0.94) in an age- and sex-adjusted model but not in a multivariable adjusted model including obesity measures with a HR of 0.95 (0.66–1.35). In genetic one-sample Mendelian randomization analysis, a 1-unit log-transformed higher plasma adiponectin was not associated with a causal risk ratio for psoriasis of 1.33 (0.77–2.32) in the CGPS. In two-sample Mendelian randomization analyses, a 1-unit log-transformed higher plasma adiponectin was not associated with causal risk ratios for psoriasis of 0.96 (0.81–1.14) in FinnGen and 1.00 (1.00–1.01) in UKB. Conclusions Low plasma adiponectin is associated with increased risk of psoriasis in age- and sex-adjusted observational analyses; however, this was not the case after adjustment for obesity measures or in causal genetic analyses.

中文翻译：

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脂联素和银屑病风险：多达 900 000 人的观察性和孟德尔随机化研究


背景 银屑病是一种慢性炎症性皮肤病，通常与肥胖有关。脂联素是脂肪组织分泌的一种抗炎蛋白激素，可能是肥胖和银屑病之间的联系。在观察性和因果遗传学研究中，我们假设低血浆脂联素与银屑病风险增加有关。方法 在观察性分析中，我们使用了来自哥本哈根一般人群研究 （CGPS） 的 30 045 名个体的血浆脂联素和银屑病信息。在单样本孟德尔随机化分析中，我们使用了来自 CGPS 的 107 308 个个体的脂联素和银屑病的遗传信息。在双样本孟德尔随机化分析中，我们使用了来自 ADIPOGen 联盟的脂联素遗传信息以及来自 FinnGen 研究和英国生物样本库 （UKB） 的 373 338 和 462 933 个体的银屑病遗传信息。结果 在观察性分析中，在年龄和性别调整的模型中，1 个单位的对数转换较高的血浆脂联素与银屑病风险比 （HR） 为 0.67（95% 置信区间：0.48-0.94）相关，但在多变量调整模型中则不相关，包括 HR 为 0.95 （0.66-1.35） 的肥胖测量。在遗传单样本孟德尔随机化分析中，1 个单位对数转化的高血浆脂联素与 CGPS 中银屑病的因果风险比为 1.33 （0.77-2.32） 无关。在双样本孟德尔随机化分析中，1 个单位对数转换的高血浆脂联素与 FinnGen 的 0.96 （0.81-1.14） 和 UKB 的 1.00 （1.00-1.01） 的银屑病因果风险比无关。 结论 在年龄和性别调整的观察分析中，低血浆脂联素与银屑病风险增加相关;然而，在调整肥胖测量或因果遗传分析后，情况并非如此。